We examined regional cerebral blood flow (rCBF) and oxygen metabolism (rCMRO2) in 10 patients with progressive dementia and amyotrophic lateral sclerosis (DALS), in 21 patients with classical amyotrophic lateral sclerosis without dementia (ALS), and in 17 controls. The mean rCBF and rCMRO2, especially in the anterior cerebral hemispheres, decreased significantly in patients with DALS. Patients with only ALS showed very mild changes in rCBF and rCMRO2 which were not significant except for the reductions in the sensorimotor area. Some rCBF and rCMRO2 values in ALS showed a significant correlation with some neurological signs indicating upper motor neuron involvement. These data suggest that hypoperfusion and oxygen hypometabolism in the anterior cerebral hemispheres have an etiological relationship with the deterioration of intellect in patients with progressive dementia and ALS. The metabolic and perfusional changes in the cerebral cortex of ALS patients are likely to depend on upper motor neuron involvement, but they are not confined to the neurons of the corticospinal tract.